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Biomedical subjects

R K Millard

Publications and source records attributed to R K Millard.

16 recordsLinked to original sources

Scope of linear estimators of tidal and occluded volumes using thoracoabdominal indications of breathing movement coordination.

The basic theory for respiratory inductive plethysmography (RIP) applications was re-examined, refined and tested. A realistic model of the RIP interpretation of respiratory mechanics related tidal volumes (VT) to a linear combination of ribcage and abdomen movements. Lissajous plots of asynchronous thoracoabdominal movements revealed their net effect equivalent to the superposition of synchronous and antipathetic respiration modes at right angles, along the principal axes specific to the combined motion. Predictors of relative changes in VT, degree of asynchrony and volume thus being occluded were developed via least squares estimation theory, with an optional validation facility. The approach enabled clinically adequate analysis of 452 h of RIP data from 29 postoperative patients. Correct identification of only seven complete apnoeas in 111 incidences of obstruction during periodic, variable, asynchronous or paradoxical natural breathing was substantiated via non-invasive airflow monitoring. The modelling helped clarify RIP limitations--the possibility of misleading indications from obese or abnormal physiques or movement artefacts degrading its otherwise nearly optimal performance. Nevertheless, our uncalibrated predictors had better theoretical basis, improved reliability and more convenient practical utility than the traditional approach of calibrating RIP by spirometry prior to non-invasive monitoring and identifying and classifying apnoeas.

Abdomen↗

Doses to fetal and maternal organs from intravenous 59FeCl3 or 57CoCl2.

Doses from intravenous intakes of 59Fe or 57Co chloride during pregnancy were estimated. Near term fetal organ doses were derived via the MIRDOSE3 newborn phantom, with mean dose/cumulated activity (S) values rescaled for compatibility with near term fetus whole body S. A detailed in vivo biodistribution database provided indications of residence times in important maternal and fetal organs. 59Fe doses to the fetus whole body from early to late pregnancy were 7-11 mGy MBq(-1) (8.5-14.3 mSv MBq(-1)), similar to that to the mother. Doses to near term fetal spleen (59 mGy MBq(-1)), liver (36), and red marrow (9) were similar or higher than to the mother. 57Co doses to fetus whole body from early to late pregnancy were 0.7-3.3 mGy MBq(-1) (2.5-8.2 mSv MBq(-1)), similar or higher than to the mother. Doses to near term fetal small intestine (34 mGy MBq(-1)). liver (4.7) and red marrow (2.7) were similar or higher than to the mother.

Body Burden↗

Key to better qualitative diagnostic calibrations in respiratory inductive plethysmography.

Least-squares estimates for coefficients of linear models that predict tidal volume (VT) via respiratory inductive plethysmography (RIP) are given. The qualitative diagnostic calibration sum formula M(RC + KAbd) arises for idealized thoracoabdominal co-ordination within this model-fitting framework. For a normal synchronous breath K is then optimally determined from the ratio of its associated ribcage (RC) and abdomen (Abd) movement standard deviations, not from a ratio that applied to a previously measured breath. M merely rescales relative changes in (RC + KAbd) to absolute changes in VT for correct proportioning. RC and Abd move in complete antipathy during an obstructive apnoea, so use of optimal K ensures (RC + KAbd) tends to zero for such unproductive breathing efforts. The interpretation is extended to more general breathing patterns by using a complementary difference expression M(RC-KAbd) to help identify any antagonistic respiratory actions. The two new constructs are equivalent to the principal components of the combined ribcage and abdomen movements. Together they demonstrate versatile capability in uncalibrated RIP applications for obstructive apnoea detection and tracking relative changes in VT during paradoxical or variable natural breathing. Calibration is appropriate for model-fitting quality assessment but otherwise usually too patient demanding, unnecessary or detrimental to prediction monitoring efficacy.

Apnea↗

Assessing thoracoabdominal asynchrony.

The traditional method of derivation of phase difference between ribcage and abdomen breathing movements from a Lissajous plot is shown to be unsatisfactory for assessing the degree of asynchrony. The signal processing technique of cross-correlation is introduced as a better, statistically based approach. Even so, examination of the latent structure of a Lissajous figure leads to the concept of movement sum and difference components along its principal axes. This more general form of analysis is used for indicating relative changes in tidal volume during postoperative monitoring of Cheyne-Stokes breathing with obstructive apnoea, as well as tracking the degree of asynchrony. The theoretical and practical limitations of inductive plethysmography calibrations are such that the proposed methods of uncalibrated non-invasive respiratory monitoring are also preferable as research tools.

Apnea↗

Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer.

Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq(-1) were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq(-1) for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq(-1). Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

Brain↗

Progress in non-invasive respiratory monitoring using uncalibrated breathing movement components.

The theory for optimal linear combination of uncalibrated breathing movements was developed and applied in non-invasive respiratory monitoring situations for assessment. 16 patients were monitored overnight for respiratory depression during postoperative pain treatment. Intranasal/extra-oral airway pressure monitoring and pulse oximetry signals were recorded at 50 Hz. Respiratory inductive plethysmography (RIP) provided guidance to nurses regarding sensitivity settings of the pressure device during slow, shallow breathing, and vital information about breathing movements to help distinguish central from obstructive apnoeas. Subsequent analysis showed that the principal components of the standardized RIP signals would be helpful in any automated identification of pressure indicator false alarms and could provide a simple means for supplementary breath classification. The sum and difference of the scaled RIP values tracked changes in tidal volume and indicated any breathing movement asynchrony or paradox associated with obstructions. A construction was developed for emulating RIP calibration predictions of relative changes in tidal volume to within about 1%, so that invasive or demanding monitoring preparations could be by-passed altogether. The necessary signal combination and linearcalibration model background is reviewed for this simple formulation, which arises from component analysis and least squares regression. The methods are illustrated for definitive non-invasive postoperative monitoring and calibration situations. Theoretical and physiological reasons for preferring the use of balanced ribcage and abdomen contributions to overall tidal volume are presented that also help clarify the greater limitations of traditional RIP monitoring practices.

Analgesics, Opioid↗

Empirical estimators of gamma fits to tracer-dilution curves and their technical basis and practical scope.

A gamma fit facilitates smoothing and extrapolation of distorted tracer-dilution curves in blood flow studies. Theoretically based empirical estimators were developed as simple alternatives to direct regression approaches from simulated gamma distributions with a wide range of shape asymmetry. Key curve features of peak height p, full width w at half peak height, rising and falling limb inflection tangents and asymmetry of the peak time with respect to the p/2 height occurrences were related to the parameters of the distribution by multiple linear regression after suitable transformations. The product pw was simply related to the total area A under the curve, pw/A being 0.93 +/- 0.01 in 70 cardiac output determinations from ten surgical patients. Shape and scale parameters were closely related to the standard deviation, inflection point properties and w for the curves. Mensuration devices suitable for cardiac output computers were developed that calculated total areas from incomplete portions under gamma curves and by-passed the need for parameter estimation. There was limited point in estimating the distribution parameters just to derive particle transit times, because of the ad hoc nature of the fitting form, which did not allow for the back-dispersion by Brownian motion of tracer molecules diluting in blood flow. Nonetheless, the accuracy of area prediction using a gamma fit was adequate for most clinical purposes and comparable to that via the random walk function, giving good insight to established results and computing procedures.

Algorithms↗

Bootstrap resampling: a powerful method of assessing confidence intervals for doses from experimental data.

Bootstrap resampling provides a versatile and reliable statistical method for estimating the accuracy of quantities which are calculated from experimental data. It is an empirically based method, in which large numbers of simulated datasets are generated by computer from existing measurements, so that approximate confidence intervals of the derived quantities may be obtained by direct numerical evaluation. A simple introduction to the method is given via a detailed example of estimating 95% confidence intervals for cumulated activity in the thyroid following injection of 99mTc-sodium pertechnetate using activity-time data from 23 subjects. The application of the approach to estimating confidence limits for the self-dose to the kidney following injection of 99mTc-DTPA organ imaging agent based on uptake data from 19 subjects is also illustrated. Results are then given for estimates of doses to the foetus following administration of 99mTc-sodium pertechnetate for clinical reasons during pregnancy, averaged over 25 subjects. The bootstrap method is well suited for applications in radiation dosimetry including uncertainty, reliability and sensitivity analysis of dose coefficients in biokinetic models, but it can also be applied in a wide range of other biomedical situations.

Confidence Intervals↗

Inductive plethysmography components analysis and improved non-invasive postoperative apnoea monitoring.

Twenty-nine patients were monitored overnight for breathing distress patterns during postoperative analgesia. Nasal flow apnoea monitoring and pulse oximetry data were recorded at 50 Hz. Respiratory inductive plethysmography (RIP) tracked tidal volume (TV) thoracoabdominal motion, and supplemented the flow monitoring by identifying detected apnoea type. TVs were computed from linear combinations of the RIP signals, but calibrations showed that multiple regression approaches with fitting errors <1% had highly variable coefficients and estimate precisions. Simple least squares theory showed that unstable parameter calculation and coefficient variation with signal conditions were inherent in RIP calibration models. Principal components (PC) methods were well suited to mitigating these problems because the RIP signals were highly correlated. The two PCs tracked the relative changes in TVs and indicated the degree of signal asynchrony, enabling improved uncalibrated monitoring. For accurately measuring RIP phase differences, the cross-correlation function was calculated. A simple version of PC analysis is developed, avoiding matrices, to help clarify how RIP calibration problems can be addressed. The methods are illustrated for calibration in normal breathing, and for postoperative monitoring during Cheyne-Stokes breathing. Sum and difference combinations of the RIP signals could discriminate central from obstructive apnoeas to help improve flow monitoring efficacy on-line.

Analgesia↗

Indicator-dilution dispersion models and cardiac output computing methods.

The general theory of indicator-dilution methods provides a basis for computing improved cardiac output estimates. Interpretation is via indicator-dispersion modeling with Brownian motion of drifting particles. Detected curves indicate the distribution of passage times from the injection site: the local density random walk (LDRW) function of a Wiener process. Fitting the LDRW to 70 dye curves by nonlinear regression for examples, I show how all possible undistorted curves can, in principle, be simulated. I show via semilogarithmic plots that conventional exponential decay constructs systematically underestimate cardiac output by up to 8%. To help reconcile the predictions of LDRW-fitted dilution curves and contemporary practice, I show how curve-shape asymmetry (skewness) dramatically affects the enclosed areas. Mean transit times may overestimate blood volumes by 15-100% in very skewed thermodilution curves if the dispersion effects are overlooked. Triangle constructions, which accounted for hundreds of experimental findings, also have theoretical explanations. Curve-fitting methods reduce the extrapolation biases inherent in many computers and in any respiration-induced artifacts. Compatibility of cardiac output predictions from various dilution methods and modules becomes feasible.

Artifacts↗

Self-tuning adaptive control of induced hypotension in humans: a comparison of isoflurane and sodium nitroprusside.

Induced hypotension is commonly used during surgery to decrease arterial pressure. Sodium nitroprusside and isoflurane are well-known hypotensive agents. The use of self-tuning adaptive control of induced hypotension was assessed with the use of sodium nitroprusside and isoflurane as hypotensive agents. Nineteen surgical patients were studied during closed-loop control of hypotension induced with sodium nitroprusside. This group of patients was compared with 10 similar patients in whom infusions of sodium nitroprusside were controlled manually by an anesthesiologist. Although the results of the two studies varied, no conclusion could be drawn regarding the superiority of either manual or closed-loop control. When manual versus automatic control of isoflurane-induced hypotension was assessed in a similar fashion, the two methods of induction were found to be comparable.

Algorithms↗

Automatic arterial pressure regulation using isoflurane: comparison with manual control.

A self-tuning, closed-loop controller, based on the algorithm of Clarke and Gawthrop, was used to regulate the inspired concentration of isoflurane to reduce arterial pressure electively in 33 patients undergoing ENT surgery. The patients were allocated randomly to one of four groups and received differing doses of fentanyl and labetalol to vary the range of sensitivities to the hypotensive action of isoflurane. The performance of the controller was evaluated at two target arterial pressures (AP), by its response to simulated changes in AP and by a comparison with a further group of eight patients with manual control of AP. The controller's undershoot of AP (range 2.8 +/- 0.5-4.5 +/- 1.3 mm Hg) and % time spent within +/- 5 mm Hg of the target AP (range 83 +/- 3.4-89 +/- 2.2%) were acceptable and equalled the manual performance figures (range 3.3 +/- 0.8 mm Hg; 90 +/- 5%). The regulation of induced hypotension in all four groups was rapid, accurate, stable and reproducible.

Adolescent↗

Clonidine premedication for isoflurane-induced hypotension. Sympathoadrenal responses and a computer-controlled assessment of the vapour requirement.

The effect of single-dose clonidine premedication on the vapour requirement for isoflurane-induced hypotension in patients undergoing middle ear or nasal surgery was evaluated in an open, controlled, randomized study. Inspired isoflurane concentration was regulated by a microcomputer-based, self-tuning control program when hypotension was required. Patients given clonidine 0.6 mg by mouth 2 h before operation required a mean inspired isoflurane concentration of 2.0% to induce hypotension (mean intra-arterial pressure 50 mm Hg) compared with 3.01% in the control group (P less than 0.05). Five out of 10 patients in the control group required a supplementary dose of labetalol 5 mg i.v. to achieve satisfactory hypotension, compared with one of 10 patients given clonidine premedication (Fisher's exact probability, 0.07). A mean concentration of 1.4% isoflurane was required to maintain hypotension in the clonidine group, compared with 2.3% in the control group (P less than 0.01). Plasma adrenaline and noradrenaline concentrations did not increase during induced hypotension in each group.

Adolescent↗

On using a self-tuning controller for blood pressure regulation during surgery in man.

The generalized minimum-variance self-tuning controller of Clarke and Gawthrop has been used to adjust the flow rate of a modified Vickers Treonic IP4 syringe pump delivering phenylephrine to 20 patients undergoing lower abdominal surgery during epidural analgesia. This proved to be a very effective method of restoring and maintaining normal arterial pressure. The method has also been used to produce controlled hypotension in 18 patients undergoing plastic or neurosurgical procedures via sodium nitroprusside infusions. Valuable insight into patient responses to surgical stimuli, blood loss, fluid loads, opioids, relaxants and other agents was provided.

Anesthesia, Epidural↗